Stephanie Tuminello, Yibeltal Arega Ashebir, Chanel Schroff, Sitharam Ramaswami, Nedim Durmus, Yu Chen, Matija Snuderl, Yongzhao Shao, Joan Reibman, Alan A Arslan
{"title":"全基因组 DNA 甲基化图谱与世贸中心幸存者中的乳腺癌。","authors":"Stephanie Tuminello, Yibeltal Arega Ashebir, Chanel Schroff, Sitharam Ramaswami, Nedim Durmus, Yu Chen, Matija Snuderl, Yongzhao Shao, Joan Reibman, Alan A Arslan","doi":"10.1097/EE9.0000000000000313","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer.</p><p><strong>Methods: </strong>WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis.</p><p><strong>Results: </strong>A total of 64 WTC-exposed (32 cancer free and 32 with breast cancer) and 32 WTC-unexposed (16 cancer free and 16 with prediagnostic breast cancer) participants were included. Hypermethylated cytosine-phosphate-guanine probe sites (defined as <i>β</i> > 0.8) were more common among WTC-exposed versus unexposed participants (14.3% vs. 4.5%, respectively, among the top 5000 cytosine-phosphate-guanine sites). Cancer-related pathways (e.g., human papillomavirus infection, cGMP-PKG) were overrepresented in WTC-exposed groups (breast cancer patients and cancer-free subjects). Compared to the unexposed breast cancer patients, 47 epigenetically dysregulated genes were identified among WTC-exposed breast cancers. These genes formed a network, including Wnt/β-catenin signaling genes <i>WNT4</i> and <i>TCF7L2</i>, and dysregulation of these genes contributes to cancer immune evasion.</p><p><strong>Conclusion: </strong>WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism.</p>","PeriodicalId":11713,"journal":{"name":"Environmental Epidemiology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152787/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genome-wide DNA methylation profiles and breast cancer among World Trade Center survivors.\",\"authors\":\"Stephanie Tuminello, Yibeltal Arega Ashebir, Chanel Schroff, Sitharam Ramaswami, Nedim Durmus, Yu Chen, Matija Snuderl, Yongzhao Shao, Joan Reibman, Alan A Arslan\",\"doi\":\"10.1097/EE9.0000000000000313\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer.</p><p><strong>Methods: </strong>WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis.</p><p><strong>Results: </strong>A total of 64 WTC-exposed (32 cancer free and 32 with breast cancer) and 32 WTC-unexposed (16 cancer free and 16 with prediagnostic breast cancer) participants were included. Hypermethylated cytosine-phosphate-guanine probe sites (defined as <i>β</i> > 0.8) were more common among WTC-exposed versus unexposed participants (14.3% vs. 4.5%, respectively, among the top 5000 cytosine-phosphate-guanine sites). Cancer-related pathways (e.g., human papillomavirus infection, cGMP-PKG) were overrepresented in WTC-exposed groups (breast cancer patients and cancer-free subjects). Compared to the unexposed breast cancer patients, 47 epigenetically dysregulated genes were identified among WTC-exposed breast cancers. These genes formed a network, including Wnt/β-catenin signaling genes <i>WNT4</i> and <i>TCF7L2</i>, and dysregulation of these genes contributes to cancer immune evasion.</p><p><strong>Conclusion: </strong>WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism.</p>\",\"PeriodicalId\":11713,\"journal\":{\"name\":\"Environmental Epidemiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-06-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152787/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environmental Epidemiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1097/EE9.0000000000000313\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Epidemiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/EE9.0000000000000313","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景：据报道，受世界贸易中心（WTC）影响的人群癌症发病率增加。DNA 甲基化异常是癌症发展的一个标志。迄今为止，只有少数几项小型研究调查了世贸中心暴露与 DNA 甲基化之间的关系。本研究的主要目的是评估受世界贸易中心影响的社区成员中未患癌症者和患乳腺癌者的 DNA 甲基化情况：方法：从世界贸易中心环境健康中心诊所选取受世界贸易中心影响的妇女，在常规临床监测访问中采集外周血。参照组选自纽约大学妇女健康研究（NYU Women's Health Study），该研究是一项前瞻性队列研究，在 2001 年 11 月 9 日前采集血样。Infinium MethylationEPIC 阵列用于全局 DNA 甲基化分析，并对细胞类型组成和其他混杂因素进行了调整。注释探针用于生物通路和网络分析：共纳入了 64 名接触过世界贸易中心的参与者（32 人未患癌症，32 人患有乳腺癌）和 32 名未接触过世界贸易中心的参与者（16 人未患癌症，16 人患有诊断前乳腺癌）。高甲基化胞嘧啶-磷酸鸟嘌呤探针位点（定义为β > 0.8）在暴露于 WTC 的参与者中比未暴露于 WTC 的参与者中更为常见（在前 5000 个胞嘧啶-磷酸鸟嘌呤位点中分别为 14.3% 和 4.5%）。与癌症相关的途径（如人类乳头瘤病毒感染、cGMP-PKG）在受到 WTC 暴露的群体（乳腺癌患者和无癌症受试者）中所占比例过高。与未暴露的乳腺癌患者相比，暴露于 WTC 的乳腺癌患者中发现了 47 个表观遗传失调基因。这些基因形成了一个网络，其中包括Wnt/β-catenin信号基因WNT4和TCF7L2，这些基因的失调有助于癌症免疫逃避：结论：接触世界贸易中心可能会影响 DNA 甲基化，并可能通过免疫介导机制使接触者易患癌症。
Genome-wide DNA methylation profiles and breast cancer among World Trade Center survivors.
Background: Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer.
Methods: WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis.
Results: A total of 64 WTC-exposed (32 cancer free and 32 with breast cancer) and 32 WTC-unexposed (16 cancer free and 16 with prediagnostic breast cancer) participants were included. Hypermethylated cytosine-phosphate-guanine probe sites (defined as β > 0.8) were more common among WTC-exposed versus unexposed participants (14.3% vs. 4.5%, respectively, among the top 5000 cytosine-phosphate-guanine sites). Cancer-related pathways (e.g., human papillomavirus infection, cGMP-PKG) were overrepresented in WTC-exposed groups (breast cancer patients and cancer-free subjects). Compared to the unexposed breast cancer patients, 47 epigenetically dysregulated genes were identified among WTC-exposed breast cancers. These genes formed a network, including Wnt/β-catenin signaling genes WNT4 and TCF7L2, and dysregulation of these genes contributes to cancer immune evasion.
Conclusion: WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism.
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